Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK.

By Han C. Dan, M. Cooper, P. Cogswell, J. Duncan, J. Ting, A. Baldwin. Genes & Development, 2008

668 citations recorded by the source corpus.

While NF-kappaB is considered to play key roles in the development and progression of many cancers, the mechanisms whereby this transcription factor is activated in cancer are poorly understood. A key oncoprotein in a variety of cancers is the serine-threonine kinase Akt, which can be activated by mutations in PI3K, by loss of expression/activity of PTEN, or through signaling induced by growth factors and their receptors. A key effector of Akt-induced signaling is the regulatory protein mTOR (mammalian target of rapamycin). We show here that mTOR downstream from Akt controls NF-kappaB activity in PTEN-null/inactive prostate cancer cells via interaction with and stimulation of IKK. The mTOR-associated protein Raptor is required for the ability of Akt to induce NF-kappaB activity. Correspondingly, the mTOR inhibitor rapamycin is shown to suppress IKK activity in PTEN-deficient prostate cancer cells through a mechanism that may involve dissociation of Raptor from mTOR. The results provide insight into the effects of Akt/mTOR-dependent signaling on gene expression and into the therapeutic action of rapamycin.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9adc43f4084d353936c741f01e09e0ab1115222c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Gary D. Bader
2. Kenneth D. Aldape

In Molecular Biology

1. C. Abate-Shen
2. Gary D. Bader
3. M. Shen
4. Richard J. Gilbertson
5. Jüri Reimand
6. Kenneth D. Aldape
7. Igor Jurisica
8. Natasa Przulj

Citations in the corpus

• Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. (2015, background): “Loss of PTEN expression/activity has previously been demonstrated to induce NF-kB activity through activation of Akt/ mTOR (Dan et al., 2008), suggesting that alternativemechanisms may exist that lead to activation of this key pathway in the STEPN-RELA subgroup.”
• Molecular genetics of prostate cancer: new prospects for old challenges. (2010, background): “Moreover, analyses of TRAMP mice and cell lines have shown that nuclear IKKa can enhance prostate cancer metastasis through down-regulation of Maspin (Luo et al. 2007).”